Parenchymal-stromal cell interaction in metabolic diseases [in Japanese]
Access this Article
Search this Article
Evidence has suggested that parenchymal-stromal cell interaction is implicated in the development of a variety of metabolic diseases. In obese adipose tissue, saturated fatty acids, which are released as a danger signal from hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating macrophages, thus establishing a vicious cycle that augments adipose tissue inflammation. Histologically, macrophages aggregate to constitute crown-like structures (CLS), where they are thought to scavenge the residual lipid droplets of dead adipocytes. In obese adipose tissue, macrophage-inducible C-type lectin (Mincle) is induced in macrophages constituting CLS, the number of which is correlated with the extent of interstitial fibrosis. Mincle, when activated by an as-yet-unidentified danger signal released from dead or dying adipocytes, may play a key role in adipose tissue inflammation and fibrosis. Free fatty acids, when released from obese visceral fat depots, are transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thus developing nonalcoholic steatohepatitis (NASH). There is a unique histological feature termed "hepatic CLS (hCLS)" in the NASH liver, where macrophages aggregate to surround dead hepatocytes with large lipid droplets. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis, which suggests that hCLS serves as an origin of hepatic inflammation and fibrosis during the progression from simple steatosis to NASH. We postulate that CLS/hCLS represent the unique microenvironment for parenchymal-stromal cell interaction in metabolic diseases.
- Inflammation and Regeneration
Inflammation and Regeneration 35(4), 167-171, 2015
The Japanese Society of Inflammation and Regeneration